Quick note for Tumor suppressor RecQL5 controls recombination induced by DNA crosslinking agents

Paper: Tumor suppressor RecQL5 controls recombination induced by DNA crosslinking agents
doi: 10.1016/j.bbamcr.2014.01.005. Epub 2014 Jan 10

It is a little bit complicated to imagine how RecQL5 repairs the damage from interstrand crosslink (ICL) agent, like in this case cisplatin and mitomycin C.

RecQ-family; DNA helicase (denature DNA duplex)
- maintenance genome stability
Focus on RecQL5
- RecQL5 - tumor suppressor
- interact with Rad51- displace Rad51-ssDNA

Gap;
Precise role of RecQL5 is elusive.

Results;
1.RecQL5 is involved in DNA interstrand crosslink (cisplatin, mitomycin C) repair.
2.Phenotype of RecQL5 KO resembled to FA gene KO cells
3.RecQL5 is involved in FANCD1 (BRCA2)-dependent ICL repair
4. Disappear of Rad51-foci delayed in REQL5KO cells after MMC treatment
5. Rad54 delayed Rad51-ssDNA in HR, compare to RecQL5
6.RecQL5 sensitivity to CDDP, and delayed Rad51-ssDNA detachment.
7.RecQL5 and Rad54 have a different effect on Rad51-ssDNA detachment.
8.Suggesting the role of RecQL5 on regulating incidence and quality of ICL-induced recombination

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Cell line:

DT40

RecQL5 -- remove Rad51-ssDNA filament but it works in different way with the Rad54

RecQL5 -- showed the sensitivity toward interstrand crosslink drugs, CDDP and MMC, but not VP16, CPT, HU and gamma X-ray

Therefore, the group focused in-depth detail on how RecQL5 fix the damage from the ICL.

RecQL5 KO gave the same replication rate with the WT and the cell-cycle analysis was also comparable to the wild-type. But once, this KO was challenged by CDDP; the cell-cycle was significantly different from the WT. Then, later experiments they basically used MMC and CDDP to investigate the molecular mechanisms of DNA repair. They showed that it related through BRCA2 since the double knockout gave the same phenotype as RecQL5 knockout. While the phenotypes from the other double knockouts were different from RecQL5 knockout.

They also proposed the mechanism which RecQL5 used to resolve the damage from interstrand crosslinking agents. They proposed that it worked differently with Rad54 by removing the unnecessary Rad51 out from the ssDNA while fixing the damage generating from ICL.